A Bruker X-ray high-intensity instrumentation system is requested to enable single crystal highresolution Xray diffraction experiments for the determination of the molecular structures of proteins, nucleic acids, and higher-order assemblies. The system combines a high frequency microprocessor-controlled microfocus rotating anode X-ray generator, high-brilliance multilayer optics providing very high monochromaticity, and a 4K charged-couple device (CCD) area detector with high resolution phosphor suitable for copper wavelengths. This instrumentation will provide NIH-funded investigators with a state-of-the-art system capable of delivering the highest intensity available in an in-house Xray instrument. The new system will provide a powerful tool for structural studies to enable the research of PI's in the Chemistry and Biochemistry Department, Molecular, Cellular and Developmental Biology Department, and Materials Research Laboratory at UCSB. The instrument will be housed in a 2000 square-foot laboratory located on the fourth floor of the Chemistry and Biochemistry Department, and will replace an existing Rigaku image-plate system that was purchased in 1994 and is well behind existing state-of-the-art in the field. This laboratory includes incubators for crystal growth and laboratory space for optimal examination and manipulation of crystals prior to the diffraction experiment, and serves as a further shared resource. The investigators will utilize the instrument to conduct research in broad areas of basic medical science, including structural studies of protein-nucleic acid complexes crucial to gene regulation, of unusual collagens with important biomaterials engineering applications, of proteins central to the unfolding of the developmental program in the model organism C. elegans, and of proteins involved in two-component signaling networks mediating the responses of cells to their environments. The instrument will be managed by a staff researcher as a shared facility, under the direction of an internal advisory committee composed of a number of the PI's listed in this proposal. A recharge system will be set up to generate the funds used to cover maintenance costs. Statement of Relevance: The acquisition of a rotating anode generator and state-of-the-art CCD detector will provide a crucial tool to enable the research of a large number of NIH-funded investigators at UCSB. These projects have fundamental health relevance including the development of novel protein-based therapeutics and potential therapeutic interventions into microbial diseases and the process of oncogenesis. [unreadable] [unreadable] [unreadable]